Cystic lung lesion following transbronchial lung cryobiopsy: Case report and systematic review : Lung India

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Cystic lung lesion following transbronchial lung cryobiopsy: Case report and systematic review

Malegaonkar, Srikant Kashinath1; Sehgal, Inderpaul Singh1; Muthu, Valliappan1; Agarwal, Ritesh1; Bal, Amanjit2; Dhooria, Sahajal1,

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Lung India 40(3):p 267-270, May–Jun 2023. | DOI: 10.4103/lungindia.lungindia_429_22
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Transbronchial lung cryobiopsy (TBLC) is now widely used to sample the lung parenchyma for diagnosing diffuse lung diseases.[1] TBLC yields larger specimens than the conventional transbronchial forceps lung biopsy (TBLB) and has a diagnostic yield better than TBLB but lower than surgical lung biopsy.[2,3] Pneumothorax and bleeding are the most common complications associated with this technique.[1,4] Rarely, an acute exacerbation of the underlying interstitial lung disease (ILD) might occur after TBLC.[5] Another rare finding after TBLC is the appearance of cystic spaces in the sampled lung.[6–12] Herein, we report a case where the patient developed an acute exacerbation of ILD (AE-ILD) and a new lung cyst appeared after TBLC. We also perform a systematic review of the literature on cystic lung lesions (cysts/pneumatoceles/cavities) appearing after TBLC.


A 75-year-old man presented with dry cough and breathlessness (grade 1 on the modified Medical Research Council scale) of 4 months duration. There was no chest pain, hemoptysis, fever, anorexia, or weight loss. He had retired from a desk job and had no comorbid illness. He used to smoke cigarettes till 10 years back (20 pack-years). There was no history suggesting connective tissue disease, recent drug intake, organic or inorganic dust exposures, or history of ILD in the family. On examination, the pulse rate was 98 beats/minute, respiratory rate 16 breaths/minute, and blood pressure 130/80 mmHg. Pulse oximetric saturation was 96% on room air. There was pandigital clubbing. End-inspiratory crackles were heard on chest auscultation. The remaining physical examination was unremarkable.

Complete blood count, liver and kidney function tests, coagulation profile, and electrocardiogram were normal. Spirometry revealed a mild restrictive defect with a forced vital capacity (FVC) of 2.34 L (83% of the predicted), forced expiratory volume in one second (FEV1) of 1.94 L (77% of the predicted), and an FEV1/FVC ratio of 0.83. Antinuclear antibodies, rheumatoid factor, anti-cyclic citrullinated peptide, and anti-neutrophil cytoplasmic antibodies were not detected in the serum. Echocardiography showed normal systolic and diastolic ventricular function with an absence of pulmonary hypertension. Chest radiograph showed bilateral reticular opacities suggesting an ILD. Thin-section computed tomography (CT) of the chest revealed bilateral interlobular and intralobular septal thickening, ground glass opacities, architectural distortion, and traction bronchiectasis [Figure 1a], with an apicobasal gradient. We considered the possibilities of idiopathic pulmonary fibrosis and hypersensitivity pneumonitis.

Figure 1:
(a) Computed tomography (CT) of the chest showing the presence of ground-glass opacities, reticulation, and traction bronchiectasis predominantly in the peripheral and basal parts of the lung parenchyma. The left lower lobe does not show any cyst; (b) Chest CT performed after cryobiopsy showing a new cystic lesion in the left lower lobe (solid arrow); (c) Hematoxylin and eosin-stained section (40X magnification) of the lung biopsy showing interstitial thickening and mild lymphomononuclear infiltrate predominantly around terminal bronchioles. Inset: Lung biopsy section revealing the presence of a large pulmonary artery branch (open arrow) in the specimen; (d) Chest CT at 9 months showing the disappearance of the cyst in the left lower lobe, but increase in traction bronchiectasis and the new appearance of honeycombing

We performed TBLC under general anesthesia in the operating room; fluoroscopy was not available. A size 12 rigid tracheobronchoscope (Karl Storz SE & Co. KG, Tuttlingen, Germany) was inserted into the trachea. A flexible bronchoscope was passed through the rigid barrel. Bronchoalveolar lavage was performed from the left upper lobe. A 5-Fr Fogarty balloon was then placed into the left lower lobe bronchus. We performed TBLC using a 1.9-mm cryoprobe (900-mm length, ERBE Elektromedizin, Tubingen, Germany) introduced through the working channel of the flexible bronchoscope and activated for 4-6 seconds, as described previously.[4,13,14] Five tissue samples were obtained; three from the lateral segment, one from the superior segment, and one from an accessory segment of the left lower lobe. It was difficult to navigate the cryoprobe during biopsy as the segmental bronchi were narrowed, possibly due to lung fibrosis. Since the first four passes yielded small specimens, for the final pass, we increased the freezing time to eight seconds. There was severe bleeding from the left lower lobe after the last biopsy that flooded the airways on both sides. We controlled the bleeding by suctioning, instilling ice-cold saline and adrenaline, and inflating another Fogarty balloon in the left lower lobe bronchus. The patient-developed hypoxemia and required mechanical ventilation in the intensive care unit for one day and was subsequently extubated. We cleared the airways of blood clots during flexible bronchoscopy; there was no ongoing bleeding. Hypoxemia persisted without any fever, expectoration, orthopnea, chest pain, or limb swelling. The CT pulmonary angiogram was normal. Thin-section chest CT showed increased ground-glass opacities in both the lungs along with a new cystic lesion in the left lower lobe [Figure 1b]. Sputum examination did not show any acid-fast bacilli, Xpert MTB/RIF was negative, and cultures did not show any bacterial growth. Consequently, we attributed the lung cyst to biopsy trauma. We diagnosed an AE-ILD and administered 1-gram pulses of methylprednisolone intravenously for three days. Histopathological examination of the biopsy specimen showed lymphomononuclear infiltrate around the bronchioles with collagenous fibrosis and fibroblastic foci [Figure 1c]. One of the cryobiopsy specimens showed a large bronchial vessel [Figure 1d]. After a multidisciplinary team discussion, we made a diagnosis of fibrotic hypersensitivity pneumonitis. Hypoxemia resolved in three days and the patient was discharged. We prescribed him oral prednisolone (40 mg/day) tapered over the next four weeks to a 10mg/day dose and added oral mycophenolate mofetil (2 grams/day). The patient had no increase in breathlessness during his last follow-up visit, nine months after the TBLC. The cyst had disappeared. However, there was an increase in traction bronchiectasis and the appearance of honeycombing accompanied by a reduction in the percentage of the predicted FVC to 67%. We diagnosed the subject to have progressive fibrosing ILD and commenced nintedanib.


We searched the PubMed and EmBase databases using the search string: lung cryobiopsy AND (cyst* OR pneumatocele OR cavity OR cavitation). Our search yielded 94 citations after removing duplicates. Two authors (SKM, SD) reviewed the titles and abstracts. Finally, eight articles (one research article and 7 case reports) including 18 cases with cystic lung lesions (including the index case) were found suitable for inclusion [Table 1]. Of these, 16 (88.9%) were attributable to trauma during TBLC; two cases were due to infection. Follow-up imaging was available for 15 subjects. The cystic lesions resolved completely in 12/15 (80.0%) subjects but persisted in three after a variable duration of follow-up. In the only original article, Loor and colleagues described TBLC in 22 subjects who had received lung transplantation.[10] They recorded various types of lung opacities including ground-glass, solid, and cavitary lesions that developed after TBLC. Eleven (50%) of the 22 subjects developed lung cysts after TBLC. There was no association between the volume of the biopsied sample, or the number of specimens obtained from a single segment, and the number of post-TBLC opacities.

Table 1:
Details of the articles included in the systematic review


There are several important learning points. First, cystic spaces may appear after TBLC.[8,11,12] They might be under-reported as a CT chest is not performed routinely after TBLC. In our case, the CT chest was performed for diagnosing an unrelated complication, i.e., AE-ILD. Loor and colleagues found that about 50% of patients who undergo TBLC might develop cystic lung lesions.[10] The systematic review also revealed that about 90% of cystic lesions are attributable to biopsy trauma. In our case too, the rapid development of the lesion and its location in one of the biopsied segments suggested that it was likely a consequence of the laceration and congealing around the freezing point during cryobiopsy.[7] The surrounding rim and ground glass opacity likely represents edema and bleeding. Occasionally, cystic or cavitary lesions after TBLC may be due to infection, as seen in two patients in the systematic review. One of the patients developed a lung abscess possibly due to ongoing systemic glucocorticoids at the time of TBLC, which might have increased the risk of infection. In our case, the absence of symptoms, normal sputum examination, and improvement without antimicrobial treatment excluded an infective etiology.

Second, significant bleeding may occur during TBLC.[4] In our case, the bleeding was possibly due to the longer freezing time that we used resulting in the freezing and shearing of the proximal bronchial region as evident from the large bronchial vessel seen in the biopsied tissue. Further, we suspect that the occlusion balloon got inadvertently displaced, which led to the spillage of blood into the airways. The subsequent prolonged ventilation possibly culminated in the AE-ILD. Had we used fluoroscopy, it could have helped us avoid placing the cryoprobe too proximally.[2]

Third, the role of high-dose (pulse dose) glucocorticoids is controversial for the common AE-ILD unrelated to interventional procedures. However, high-dose glucocorticoids might be effective in the setting of an exacerbation triggered by an intervention such as TBLC. Our report is limited by the lack of follow-up imaging. The systematic review of current literature failed to yield any large study on the incidence of such lesions and their natural history. Multicenter longitudinal studies are required to confirm the findings of the current review of a small dataset.

Finally, non-IPF fibrotic ILDs can progress resulting in a decline in lung function and an increase in the radiologic signs of fibrosis. Our patient met the criteria for progressive pulmonary fibrosis (PPF) that occurred despite treatment with prednisolone and mycophenolate.[15] Progression can occur rapidly after an acute exacerbation resulting from TBLC, as has been described previously.[5] The American Thoracic Society guidelines on PPF have given a conditional recommendation for the use of nintedanib for treating ILDs with PPF.

In conclusion, lung cysts can appear after TBLC due to the biopsy trauma. Significant bleeding and AE-ILD are important complications of TBLC. Freezing times longer than six seconds are better avoided.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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Bronchoscopy; hypersensitivity pneumonitis; ILD; interstitial lung disease; lung cryobiopsy

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